Transforming growth factor β1 regulates angiotensin II type I receptor gene expression in the extravillous trophoblast cell line SGHPL-4

The angiotensin II type 1 (AT1) receptor, transforming growth factor β1 (TGFβ1) and Oncostatin M (OSM) control key pathways that may be important during placentation. Although interactions between them exist in other tissues, trophoblast cells have not been investigated. Extravillous trophoblast cells, SGHPL-4, were stimulated with 10 ng/ml TGFβ1 ± 100 ng/ml OSM for 24 h. Real-time PCR showed that AT1 expression increased 2.76-fold [95% confidence interval (CI) = 1-6.74, P = 0.05] in response to TGFβ1 and 4.21-fold (95% CI = 1.33-11.76, P = 0.03) with TGFβ1 + OSM. Luciferase reporter gene constructs containing three haplotypes of the 59 flanking region of the AT1 receptor gene were transfected into SGHPL-4 and HepG2 cells and stimulated with 0.1, 1 and 10 ng/ml TGFβ1 and 50 ng/ml OSM. Responses were dose and cell dependent. Luciferase activity increased in HepG2 cells in response to TGFβ1 alone or together with OSM (P <0.001); transcriptional activation differed between AT1 receptor gene haplotypes. In SGHPL-4 cells, luciferase activity was reduced on exposure to low concentrations of TGFβ1 or high concentrations of TGFβ1 combined with OSM (P = 0.003); the response was unaffected by haplotype. Interaction between AT1 and TGFβ1 is a novel observation in trophoblast and suggests new avenues for the study of placentation. © 2005 Oxford University Press.